The proposed studies have been designed to utilize the micropuncture technique in a systematic evaluation of uric acid transport along the length of the proximal tubule of the rat kidney. A radioassay for uric acid-2-C14 has been developed in our laboratory for this purpose. Utilizing this method, free flow micropuncture experiments have demonstrated bidirectional transport of uric acid in the proximal tubule with net reabsorption of uric acid apparent early and net secretion evident later in this nephron site. Virtually no net transport of uric acid could be detected beyond the accessible portion of the late proximal tubule. Additional studies have demonstrated that pyrazinamide inhibits the bidirectional fluxes of uric acid in the proximal tubule, with the net effect resulting in a decrease in fractional uric acid excretion. The long term goal of this project is to assess further the opposing proximal tubular transport processes by investigating those factors which might influence the separate processes. The reabsorption and secretion of uric acid will be evaluated under conditions of acute and chronic elevations of plasma $ urate concentration, acute and chronic hemodynamic alterations, variations in acid-base balance and the administration of other urate retaining and uricosuric drugs. It is anticipated that these studies may provide some insight into the nature and mechanism of the separate transport processes and their possible interrelationship.